Études sur le cancer du foie - Liver cancer studies - Studien zu Leberkrebs

ImunoBran® = BioBran®

Arabinoxylan rice bran (Biobran) suppresses the viremia level in patients with chronic HCV infection: A randomized trial

  • Hosny Salama, Eman Medhat, Magda Shaheen, Abdel-Rahman N Zekri, Tarneem Darwish and Mamdooh Ghoneum, (edited by Chris Gutch PhD.)

Current treatments for Hepatitis C virus (HCV) have severe side effects and are very expensive. There is a need to explore effective natural therapies against HCV that are less toxic and more cost-effective. In the current study, 37 chronic HCV patients were randomized into two groups and treated with either PEGylated interferon (PEG IFN) plus ribavirin (n = 21) or Biobran, an arabinoxylan from rice bran (1 g/day) (n = 16). We examined viremia, liver enzymes, interferon-γ (IFN-γ) levels in serum, and toxicity before and three months after treatment. Both groups showed a significant and similar reduction in viral load after three months of treatment relative to the baseline viral load (P <0.05). In addition, treatment with Biobran resulted in a significant increase in the level of IFN-γ (P <0.001). Patients in the PEG IFN plus ribavirin group showed fever, anaemia, thrombocytopenia, and easy fatigue. Patients in the Biobran group showed no side effects and reported good health. We conclude that Biobran is a potential novel therapeutic regimen that has a similar effect to PEG IFN plus ribavirin and is safe and cost-effective in the treatment of chronic HCV. Our finding of Biobran's efficacy against HCV infection warrants further investigation in multiple clinical trials (Clinical Trials Registration: NCT02690103).

Protective effect of low molecular fraction of MGN-3, a modified arabinoxylan from rice bran, on acute liver injury by inhibition of NF-kB and JNK/MAPK expression                                                                                                                                                       PEER REVIEWED

  • Surina Zheng, Shunsuke Sugita, Shizuka Hirai, Yukari Egashira, (edited by Chris Gutch PhD.)

D-Galactosamine (GaIN) induces acute hepatitis in experimental animals; this hepatitis has been shown to be suppressed by oral or intraperitoneal administration of modified arabinoxylan from rice bran (MGN-3), and active low molecular fraction isolated from MGN-3 (LMW). We previously reported that this protective mechanism is mediated in part by downregulation of interleukin-18 (IL-18), The present study shows for the first time that nuclear factor- κB (NF- κB), mitogen-activated protein kinase (MAPK) and CD14 are involved in the suppressive action of LMW on GaIN-induced hepatitis Wistar rats (aged 4 weeks, SLC) were intraperitoneally treated with either MGN-3 or LMW. Then, rats were given GaIN at 400 mg/kg at 1 h after the initial treatment, The serum activity of transaminases (ALT and AST) was significantly higher after GaIN treatment: these changes were attenuated by MGN-3 and LMW. Furthermore, LMW abrogated inhibitor of κB kinase (I κB) degradation induced by GaIN, and this was associated with the inhibition of NF κB activation. Moreover, phosphorylated stress-activated protein kinase/c-jun N-terminal kinase (JNK) protein expression in the liver after GaIN treatment was significantly higher, and LMW reduced this increase. We also found that GaIN treatment induced TLR4 and CD14 mRNA expression, and LMW significantly inhibited CD14 mRNA expression. These results suggest that the suppressive effects of LMW on GaIN-induced hepatitis are possibly related to inhibition of NF- κB,NK phosphorylation and CD14 expression.

An Open-label, randomized clinical trial to assess the immunomodulatory activity of a novel oligosaccharide compound in healthy adult                                   PEER REVIEWED

  • K. H. Ali, A. B. Melillo, S. M. Leonard, D. Asthana, Judi M. Woolger, A. H. Wolfson, H. R. McDaniel, J. E. Lewis, (edited by Chris Gutch PhD.)

Rice Bran Arabinoxylan Compound (RBAC) is a nutritional supplement produced by enzymatic hydrolysis of hemicellulose B derived from rice bran. Several in vitro studies and clinical reports have shown RBAC to possess promising immunomodulating effects, specifically with respect to natural killer cell and cytokine activity. The concept of a true immunomodulator is an agent possessing a broad range of activity dependent upon the existing state of health and immunity in the individual host. The present study investigated the immunomodulatory effect of RBAC in a healthy adult human population over 60 days by assessing changes in natural killer cell cytotoxicity (NKCC) and cytokines and growth factors. Subjects participated in a two-group, randomized intervention, where one group (n=10) consumed 1 gram/day and the other (n=10) consumed 3 gram/day. Safety and tolerability of RBAC were assessed with total bilirubin, total protein, creatinine, and liver function tests.

Chemopreventive Properties of Dietary Rice Bran: Current Status and Future Prospects PEER REVIEWED

  • Angela J. Henderson, Cadie A. Ollila, Ajay Kumar, Erica C. Borresen, Komal Raina, Rajesh Agarwal and Elizabeth P. Ryan. (edited by Chris Gutch PhD.)

Emerging evidence suggests that dietary rice bran may exert beneficial effects against several types of cancer, such as breast, lung, liver, and colorectal cancer. The chemopreventive potential has been related to the bioactive phytochemicals present in the bran portion of the rice such as ferulic acid, tricin, B-sitosterol, y-oryzanol, tocotrienols/tocopherols, and phytic acid.

Studies have shown that the anticancer effects of the rice bran-derived bioactive components are mediated through their ability to induce apoptosis, inhibit cell proliferation, and alter cell cycle progression in malignant cells. Rice bran bioactive components protect against tissue damage through the scavenging of free radicals and the blocking of chronic inflammatory responses.

Rice bran phytochemicals have also been shown to activate anticancer immune responses as well as affecting the colonic tumour microenvironment in favour of enhanced colorectal cancer chemoprevention. This is accomplished through the modulation of gut microflora communities and the regulation of carcinogen metabolizing enzymes. In addition, the low cost of rice production and the accessibility of rice bran make it an appealing candidate for global dietary chemoprevention. Therefore, the establishment of dietary rice bran as a practical food-derived chemopreventive agent has the potential to have a significant impact on cancer prevention for the global population. 

Suppressive Effect of Modified Arabinoxylan from Rice Bran (MGN-3) on D-Galactosamine-Induced IL-18 Expression and Hepatitis in Rats                   PEER REVIEWED

  • S. Zheng, H. Sanada, H. Dohi, S. Hirai and Y. Egashira, (edited by Chris Gutch PhD.)

We investigated in this study the effect of modified arabinoxylan from rice bran (MGN-3) and its fractions on D-galactosamine (D-GalN)-induced IL-18 expression and hepatitis in rats. Male Wistar rats were pre-treated with MGN-3 or fractions of the MGN-3 hydrolysate, or with saline 1 h before administering D-GalN (400 mg/kg B.W.). The serum transaminase activities, IL-18 mRNA expression level in the liver and IL-18 concentration in the serum were determined 24h after injecting D-GalN. Both the oral and intraperitoneal administration of MGN-3 (20 mg/kg B.W.) alleviated D-GalN-induced hepatic injury under these experimental conditions. The low-molecular-weight fraction (LMW) of MGN-3 showed the strongest protective effect on D-GalN-induced liver injury, its main sugar component being glucose. Moreover, the D-GalN-induced IL-18 expression was significantly reduced by treating with MGN-3 and LMW. The results suggest that MGN-3 and LMW could provide significant protection against D-GalN liver injury, and that IL-18 might be involved in their protective influence.

The clinical effectiveness of BioBran in immunotherapy for patients with hepatitis B

  • Dr. Tran Thi Minh Phuong, (edited by Chris Gutch PhD.)

Hepatitis B virus (HBV) infection is a serious global health problem with devastating consequences of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Antiviral therapy has been the primary treatments to date. However, conventional treatment has undesirable side-effects and continuous treatment can lead to the development of resistance. In addition, antiviral medicines are costly, thousands of dollars per year, and are not widely available in many countries, especially in the developing world. BioBran is a food supplement that is combined with conventional treatment to improve the outcome of the disease. There were 3 cases of viral B hepatitis patients who have treated by the combination of conventional antiviral therapy and BioBran were described. In these cases, blood samples were taken to measure liver function and immunopotency, and the results were compared with changes in clinical and image condition. Improvements were noted in most of the cases. Finally, some remarks were provided to enhance the effectiveness of treatment progress.

Biobran/MGN-3, an arabinoxylan rice bran, enhances NK cell activity in geriatric subjects: A randomized, double-blind, placebo-controlled clinical trial

  • AHMED F. ELSAID, MAGDA SHAHEEN and MAMDOOH GHONEUM, (edited by Chris Gutch PhD.)

Abstract. Aging is associated with a decline in natural killer (NK) and natural killer T (NKT) cell function that may contribute to increased susceptibility to malignancy and infection. A preliminary investigation was conducted examining the hypothesis that arabinoxylan rice bran (Biobran/MGN-3), a denatured hemicellulose with known immunomodulatory activity, could counteract this decline in NK/NKT cell activity in geriatrics. A total of 12 healthy geriatric subjects of both sexes and over 56 years old, participated in a randomized, double-blind, placebo-controlled clinical trial. A total of six subjects served as control and six subjects ingested Biobran/MGN-3 (500 mg/day) for 30 days. The effect of Biobran/MGN-3 supplementation on NK/NKT cell activity was assessed using the degranulation assay. All study subjects were monitored for the development of any inadvertent side effects. In addition, the pharmacological effects of Biobran/MGN-3 on blood cell components and liver and kidney functions were also assessed. Results demonstrated that Biobran/MGN-3 had no effect on the total percentage of NK cells, however it enhanced the cytotoxic activity of induced NK cell expression of cluster of differentiation 107a, when compared with baseline values and with the placebo group (P<0.05). Furthermore, there were no side effects observed, indicating that Biobran/MGN-3 supplementation was safe at the utilized dosage and for the duration of administration. Various additional beneficial effects were observed, including improved mean corpuscular volume and reduced hepatic aspartate aminotransferase enzyme levels, which suggested improved liver function. It was concluded that Biobran/MGN-3 induces a significant increase in NK activity which may increase resistance to viral infections and cancers in the geriatric population.

However, additional clinical trials should be conducted in the future to verify these findings.

Can a standardized plant immunomodulator (rice bran arabinoxylan concentrate/MGN-3) increase the effects of MEK and BRAF inhibitors with clinical benefit? Case report of a patient with carcinoma in biliary duct

  • Tibor Hajto, (edited by Chris Gutch PhD.)

Background: Targeting hyperactive mitogen-activated protein kinase (MAPK) signalling cascade has proven to be an effective treatment for a variety of different cancers. Using an important member of this cascade, namely MEK (mitogen activated extracellular signal regulation kinase) inhibitors, the clinical responses are often transient and complete remission is rarely observed. Outgrowth of resistant clones within progressed tumours appears to be inevitable. Recent immunological and clinical observations suggest that in background of this resistance the tumour-.induced disturbance of immunoregulation at least in part may play a role. Namely, it was shown that growth factor receptor signalling pathway inhibitors can increase the immune sensitivity of tumour cells, but they can't activate the down regulated immune effectors. Consequently, the combination of MAPK cascade signalling pathway inhibitors and the immune effectors activating immunomodulators may be a promising new strategy. Material and methods: In a now 59 years old patient with inoperable (BRAF-mutant) low differentiated adenocarcinoma of biliary ducts after 30GY radiotherapy and two cycles (Gemcitabin+ Cisplatin) chemotherapy a rapid progression of lung, liver and brain metastases were by CT and MR established. Thereafter, a treatment with BRAF+MEK inhibitors (2x150 mg dabrafenib and 1 x 2 mg trametinib) was started. These inhibitors were combined with daily 45 mg/kg rice bran arabinoxylan concentrate (using Biobran/MGN-3) which was shown to be a pathogenic associated molecular pattern (PAMP)-like molecule and can stimulate the type-1 innate immune cells against tumour cells. Results: After the chemotherapy and prior to the start of second line treatment, the patient had a nearly terminal state of her rapidly progressive disease. Eight months after the combination of MEK / BRAF inhibitor and immunomodulator therapy nearly complete remissions of all metastases was established in CT and MR. Conclusion: This case report may support a hypothesis that MEK / BRAF inhibitors and type-1 immune cells activating immunomodulators together may synergistic inhibit the tumour growth. Further clinical investigations are necessary to clarify this question.

The Clinical Significance of BioBran in the Immunotherapy for Cancer

  • Yasushi Okamura, (edited by Chris Gutch PhD.)

The clinical treatments for cancer were surgery, radiotherapy, and chemotherapy with anticancer drugs. For surgery, even if the procedure used is highly sophisticated, cancer cells may be transported to other organs via the vascular or lymph system. For radiotherapy, although it destroys cancer tissues it may also damage the surrounding functioning tissues. Anticancer drugs may destroy cancer cells as well as normally functioning cells of other organs.

Consequently, these drawbacks of the three types of treatments must be recognized when addressing cancer patients. This is where immunotherapy counts. The author has been working with immunotherapy for 25 years, and this time chose combination therapy with BioBran (rice bran arabinoxylan derivative), and BRP (Bio-Reproducing Protein) intravenously.

Case 1. K. M. 67-year-old, M. Liver cancer with intestinal metastasis

Case 2. M. O. 65-year-old, M. Liver cancer

Case 3. F. M. 71-year-old, F. Liver cancer

Case 4. H. H. 76-year-old, F. Lung cancer

Case 5. T. O. 58-year-old, M. Colorectal cancer with liver metastasis

Above five cases, blood samples were taken once a month to measure tumour markers and immunopotency, and the results were compared with the change in clinical conditions. As a result, improvements were noted in all the cases.

The Effect of a Hydrolyzed Polysaccharide Dietary Supplement on Biomarkers in Adults with Nonalcoholic Fatty Liver Disease

  • John E. Lewis , Steven E. Atlas, Oscar L. Higuera, Andrea Fiallo, Ammar Rasul, Ashar Farooqi, Olga Kromo, Laura A. Lantigua, Eduard Tiozzo , Judi M. Woolger, Sharon Goldberg, Armando Mendez , Allan E. Rodriguez, and Janet Konefal, (edited by Chris Gutch PhD.)

The primary objective of the study was to evaluate the effect of a hydrolysed polysaccharide, Rice Bran Arabinoxylan Compound (RBAC), on biomarkers in adults with non-alcoholic fatty liver disease (NAFLD). A 90-day randomized double-blind placebo-controlled trial examined the effect of RBAC on complete blood count, liver enzymes, lipids, oxidative stress markers, cytokines, and growth factors. Twenty-three adults with NAFLD were enrolled and randomly assigned to one of the two study conditions (n = 12 RBAC and n = 11 placebo) and consumed 1 gram/day of either compound for 90 days. Subjects were assessed at baseline and 45 and 90 days. No adverse effects were reported. Alkaline phosphatase significantly decreased (−3.1%; SD = 19.9; F[1, 19] = 5.1, p = 0.03) in the RBAC group compared to placebo. Percent monocytes (17.9%; SD = 18.3; F[1, 19] = 5.9, p = 0.02) and percent eosinophils (30.6%; SD = 30.5; F[1, 19] = 12.3, p < 0.01) increased in the RBAC group. IFN-γ (156%; SD = 131.8; F[1, 19] = 4.2, p = 0.06) and IL-18 (29.1%; SD = 64; F[1, 19] = 5.3, p = 0.03) increased in the RBAC group compared to placebo. Other improvements were noted for platelets, neutrophils, neutrophil-lymphocyte ratio, γ-glutamyl transferase, and 4-hydroxynonenal. RBAC had beneficial effects on several biomarkers that add to the known immunomodulatory activities of RBAC, which may be promising for people with NAFLD. 

Arabinoxylan rice bran (MGN-3/Biobran) enhances radiotherapy in animals bearing Ehrlich ascites carcinoma

  • Nariman K. Badr El-Din,*, Said K. Areida , Kvan O. Ahmed and Mamdooh Ghoneum, (edited by Chris Gutch PhD.)

This study examines the ability of arabinoxylan rice bran (MGN-3/Biobran) to enhance the anti-cancer effects of fractionated X-ray irradiation of Ehrlich solid tumor-bearing mice. Swiss albino mice bearing tumors were exposed to the following: (i) Biobran treatment (40 mg/kg/day, intraperitoneal injections) beginning on day 11 post-tumor cell inoculation until day 30; (ii) ionizing radiation (Rad) 2 Gy at three consecutive doses on days 12, 14 and 16; or (iii) Biobran + Rad. Final tumor weight was suppressed by 46% for Biobran, 31% for Rad and 57% for the combined treatment (Biobran + Rad) relative to control untreated mice. Biobran and Rad also arrested the hypodiploid cells in the sub-G1-phase, signifying apoptosis by +102% and +85%, respectively, while the combined treatment induced apoptosis by +123%, with similar results in the degree of DNA fragmentation. Furthermore, Biobran + Rad upregulated the relative gene expression and protein level of p53 and Bax in tumor cells, down-regulated Bcl-2 expression, and increased the Bax/Bcl-2 ratio and caspase-3 activity, with the combined treatment greater than for either treatment alone. Additionally, the combined treatment modulated the decrease in body weight, the increase in liver and spleen weight, and the elevation of liver enzymes aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase to be within normal values. We conclude that Biobran enhances radiation therapy-induced tumor regression by potentiating apoptosis and minimizing toxicities related to radiation therapy, suggesting that Biobran may be useful in human cancer patients undergoing radiotherapy and warranting clinical trials.

Chemopreventive role of arabinoxylan rice bran, MGN-3/Biobran, on liver carcinogenesis in rats                                                                                                        PEER REVIEWED

  • Nariman K. Badr El-Din, Doaa A. Ali, Reem Othman, Samuel W. French, Mamdooh Ghoneum, (edited by Chris Gutch PhD.)

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and one of the most lethal. MGN-3/Biobran is a natural product derived from rice bran hemicelluloses and has been reported to possess a potent anticancer effect in a clinical study of patients with HCC. The current study examines the mechanisms by which Biobran protects against chemically induced hepatocarcinogenetic in rats. The chemical carcinogen used in this study is N-nitrosodiethylamine (NDEA) plus carbon tetrachloride (CCl4). Rats were treated with this carcinogen, and the animals were pre-treated or post treated with Biobran via intraperitoneal injections until the end of the experiment. Treatment with Biobran resulted in: 1) significant alleviation of liver preneoplastic lesions towards normal hepatocellular architecture in association with inhibition of collagen fibre deposition; 2) arrest of cancer cells in the sub-G1 phase of the cell cycle; 3) increased DNA fragmentation in cancer cells; 4) down-regulated expression of Bcl-2 and up-regulated expression of p53, Bax, and caspase-3; and 5) protection against carcinogen-induced suppression of IkappaB-alpha (IκB-α) mRNA expression and inhibition of nuclear factor kappa-B (NF-κB/p65) expression. Additionally, the effect of Biobran treatment was found to be more significant when supplemented prior to carcinogen-induced hepatocarcinogenetic as compared to posttreatment. We conclude that Biobran inhibits hepatocarcinogenetic in rats by mechanisms that include induction of apoptosis, inhibition of inflammation, and suppression of cancer cell proliferation. Biobran may be a promising chemo-preventive and chemotherapeutic agent for liver carcinogenesis